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Mesoporous silica-based nano-drug delivery system capable of regulating drug release as well as construction and application of nano-drug delivery system

A technology of mesoporous silica and nano-drugs is applied in the fields of drug delivery, drug combination, and inactive medical preparations, etc. It can solve the problems of difficult to achieve precise drug release, complicated preparation of drug delivery systems, and long time-consuming.

Active Publication Date: 2020-02-25
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The existing drug delivery systems based on mesoporous silica mainly have the following problems: I. In terms of system construction, the construction of drug delivery systems still has shortcomings such as complicated preparation and long time consumption.
III In terms of drug release, it is difficult for the drug delivery system to achieve precise drug release

Method used

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  • Mesoporous silica-based nano-drug delivery system capable of regulating drug release as well as construction and application of nano-drug delivery system
  • Mesoporous silica-based nano-drug delivery system capable of regulating drug release as well as construction and application of nano-drug delivery system
  • Mesoporous silica-based nano-drug delivery system capable of regulating drug release as well as construction and application of nano-drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] (1) 7μM L -1 SI was added to EDC and NHS at a molar ratio of 1:1 into PBS at pH=7.4, and incubated at 37°C for 20 minutes to obtain carboxyl-activated SI.

[0085] (2) Mix the above-mentioned activated SI with 0.5mgmL -1 The aminated MSNP was shaken and incubated at 37°C for 6h to obtain MSNP-SI.

[0086] (3) Mix the MSNP-SI obtained above with 8 μM L -1 SM 1 , 8μM L -1 SM 2 K, incubated at 37°C for 4h to obtain linearly polymerized MSNPs.

[0087] (4) Mix the above-mentioned linear polymerized MSNP with 8 μM L -1 SM 3 , 8μM L -1 SM 4 , and incubated at 37° C. for 10 h to prepare DNA-wrapped MSNP (MSNP@DNA).

Embodiment 2

[0089] The nano-drug delivery system based on mesoporous silica constructed in Experimental Example 1 of the present invention was characterized by transmission electron microscopy.

[0090] (1) Take 10 μL of the MSNP@DNA sample prepared in Example 1 and add it dropwise to the carbon support film copper grid, let it stand for 10 minutes, absorb the solution with filter paper, and dry the copper grid with an infrared lamp.

[0091] (2) Observing the sample prepared above with a transmission electron microscope to observe its morphology. Such as figure 2 As shown, before unwrapping, MSNP has a porous structure and can load small molecule drugs; after DNA wrapping, the surface of MSNP has a shell layer with a thickness of ~10nm, indicating that DNA has successfully wrapped MSNP. Using 10mM glutathione (GSH) to incubate MSNP@DNA for 5h, it was found that the surface shell of MSNP disappeared, which indicated that GSH could break the disulfide bond and cleave the DNA shell. This...

Embodiment 3

[0093] In this experiment, ultraviolet-visible light spectroscopy was used to evaluate the loading of MSNP on chemotherapeutic drug DOX.

[0094] (1) drug load

[0095] 10mL0.5 mgmL -1 MSNP with 20 μM L -1 DOX was shaken and incubated at 37°C for 10 h, centrifuged and washed three times to obtain DOX-loaded MSNPs.

[0096] (2) Ultraviolet-visible light spectrum measurement

[0097] MSNP, DOX and MSNP-DOX@DNA were scanned in the range of 300-700nm by UV-visible spectroscopy, and their absorption characteristic peaks were observed.

[0098] (3) Results

[0099] Such as image 3 As shown, MSNP-DOX@DNA and DOX have the characteristic peak of DOX at 485nm, indicating that MSNP is successfully loaded with the chemotherapy drug DOX.

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Abstract

The invention discloses a mesoporous silica-based nano-drug delivery system capable of regulating drug release and a construction method of the mesoporous silica-based nano-drug delivery system, and the construction method comprises the following steps: adding carboxylated DNA (SI), EDC and NHS into PBS for incubation to obtain carboxyl-activated SI; then, adding aminated mesoporous silica (MSNP)for incubation, and obtaining SI bound MSNP (MSNP-SI); then adding SM1 and SM2K, and carrying out incubation so as to obtain linearly polymerized MSNP; finally, adding SM3 and SM4 for incubation, andobtaining DNA wrapped MSNP. The construction method disclosed by the invention is simple and convenient, rich in raw material source and low in production cost. The drug delivery system is used for cancer treatment, shows excellent biocompatibility, avoids the problems of drug leakage, biotoxicity and the like, enhances the drug delivery efficiency, increases the cellular uptake rate, regulates and controls the accurate release of drugs, and realizes the accurate treatment of cancer. The drug delivery system disclosed by the invention does not contain any irritant component, does not have toxic or side effect, and has potential application value in the aspect of cancer treatment.

Description

technical field [0001] The invention belongs to the field of drug delivery, and relates to a mesoporous silica-based nanometer drug delivery system capable of regulating drug release and its construction and application. Background technique [0002] Nanomedicine is a new type of drug formulation, which can be aggregated to the tumor site due to enhanced penetration and retention effects. By modifying the targeting ligands and optimizing the size and surface properties of the nanocarriers, the blood circulation time of the nanocarrier delivery system in the body can be prolonged, its biodistribution can be improved, the accumulation at the tumor site can be promoted, and the cells can be increased. intake, thereby enhancing the efficacy of the drug. [0003] Due to their numerous excellent properties, such as direct synthesis, tunable pore size, easy surface functionalization, biodegradability, and simultaneous loading of multiple drugs, mesoporous silica nanoparticles have...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K9/52A61K45/00A61K47/26A61K47/04A61P35/00
CPCA61K9/5115A61K9/5123A61K9/5192A61K45/00A61P35/00
Inventor 裴昊肖明书李丽
Owner EAST CHINA NORMAL UNIV
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